A novel hypothesis for hCG as a major control factor for estrogen production in the human feto-placental unit is presented. Preliminary data demonstrating estradiol inhibition of hCG output in vitro in suspensions of placental cells at 100 ng/ml suggests that hCG may be controlled by feedback inhibition by estradiol at the level of the placental cell. HCG appears to control estrogen production in the feto-placental unit not only by stimulating output of estrogen precursors by the fetal adrenal but also by stimulating an increase in placental aromatase. The physiology involved in estrogen production may be unique to the human and, perhaps, the great apes. In vitro studies of isolated cell suspensions from the human placenta focus on control factors for production of hCG, estradiol, progesterone, prostaglandin E, and prostaglandin F. There is evidence that the control mechanisms for these hormones may be intertwined making simultaneous studies cost effective. The methods of short-term classic incubation and superfusion will be used to study the effects of dibutyryl cyclic AMP, potassium ion, testosterone, androstenedione, dehydroepiandrosterone sulfate, estriol, and estrone, as well as hCG, estradiol, progesterone, prostagladin E2, and prostaglandin F2 alpha on output of hCG, estradiol, progesterone, prostaglandin E2, and prostaglandin F2 alpha. Hormone interactions and effects of metabolic inhibitors will also be studied. These investigations are pertinent to health care needs in pregnancy. Demonstration of a negative feedback relationship between estrogens and hCG may lead to use of hCG determinations in conjunction with estriol determinations in monitoring diabetic pregnancy and other high risk pregnancies and in determining the cause of low or high estrogen production by the feto-placental unit. The results of these investigations may also be pertinent to health care in trophoblastic disease and toxemia of pregnancy.